We present a consensus document that proposes a standardized case definition and diagnostic guidelines for evaluation of adults and children with suspected encephalitis. In addition, areas of research priority, including host genetics and selected emerging infections, are discussed.

Background. Encephalitis continues to result in substantial morbidity and mortality worldwide. Advances in diagnosis and management have been limited, in part, by a lack of consensus on case definitions, standardized diagnostic approaches, and priorities for research.

Methods. In March 2012, the International Encephalitis Consortium, a committee begun in 2010 with members worldwide, held a meeting in Atlanta to discuss recent advances in encephalitis and to set priorities for future study.

Results. We present a consensus document that proposes a standardized case definition and diagnostic guidelines for evaluation of adults and children with suspected encephalitis. In addition, areas of research priority, including host genetics and selected emerging infections, are discussed.

Conclusions. We anticipate that this document, representing a synthesis of our discussions and supported by literature, will serve as a practical aid to clinicians evaluating patients with suspected encephalitis and will identify key areas and approaches to advance our knowledge of encephalitis.

Rabies is a fatal encephalitis caused by lyssaviruses. Evidence of lyssavirus circulation has recently emerged in Southeast Asian bats. A cross-sectional study was conducted in Thailand to assess rabies-related knowledge and practices among persons regularly exposed to bats and bat habitats. The objectives were to identify deficiencies in rabies awareness, describe the occurrence of bat exposures, and explore factors associated with transdermal bat exposures.

Methods

A survey was administered to a convenience sample of adult guano miners, bat hunters, game wardens, and residents/personnel at Buddhist temples where mass bat roosting occurs. The questionnaire elicited information on demographics, experience with bat exposures, and rabies knowledge. Participants were also asked to describe actions they would take in response to a bat bite as well as actions for a bite from a potentially rabid animal. Bivariate analysis was used to compare responses between groups and multivariable logistic regression was used to explore factors independently associated with being bitten or scratched by a bat.

Findings

Of 106 people interviewed, 11 (10%) identified bats as a potential source of rabies. A history of a bat bite or scratch was reported by 29 (27%), and 38 (36%) stated either that they would do nothing or that they did not know what they would do in response to a bat bite. Guano miners were less likely than other groups to indicate animal bites as a mechanism of rabies transmission (68% vs. 90%, p = 0.03) and were less likely to say they would respond appropriately to a bat bite or scratch (61% vs. 27%, p = 0.003). Guano mining, bat hunting, and being in a bat cave or roost area more than 5 times a year were associated with history of a bat bite or scratch.

Rabies is a fatal encephalitis caused by lyssaviruses. Evidence of lyssavirus circulation has recently emerged in Southeast Asian bats. We surveyed persons regularly exposed to bats and bat habitats in Thailand to assess rabies‐related knowledge and practices. Targeted groups included guano miners, bat hunters, game wardens, and residents/personnel at Buddhist temples where mass bat roosting occurs. Of the 106 people interviewed, 11 (10%) identified bats as a source of rabies. History of a bat bite/scratch was reported by 29 (27%), and 38 (36%) expressed either that they would do nothing or that they did not know what they would do in response to a bat bite. Guano miners were less likely than other groups to indicate animal bites as a mechanism of transmission (68% vs. 90%, p=0.03) and were less likely to say they would respond appropriately to a bat bite or scratch (61% vs. 27%, p=0.003). These findings indicate a need for educational outreach in Thailand to raise awareness of bat rabies, promote exposure prevention, and ensure health‐seeking behaviors for bat‐inflicted wounds, particularly among at‐risk groups.

To provide molecular and virologic evidence that domestic dog rabies is no longer enzootic to the United States and to identify putative relatives of dog-related rabies viruses (RVs) circulating in other carnivores, we studied RVs associated with recent and historic dog rabies enzootics worldwide. Molecular, phylogenetic, and epizootiologic evidence shows that domestic dog rabies is no longer enzootic to the United States. Nonetheless, our data suggest that independent rabies enzootics are now established in wild terrestrial carnivores (skunks in California and north-central United States, gray foxes in Texas and Arizona, and mongooses in Puerto Rico), as a consequence of different spillover events from long-term rabies enzootics associated with dogs. These preliminary results highlight the key role of dog RVs and human–dog demographics as operative factors for host shifts and disease reemergence into other important carnivore populations and highlight the need for the elimination of dog-related RVs worldwide.

The prevalence of neutralizing antibody against West Caucasian bat virus (WCBV) in Miniopterus bats collected in Kenya ranged from 17% to 26%. Seropositive bats were detected in 4 of 5 locations sampled across the country. These findings provide evidence that WCBV, originally isolated in Europe, may emerge in other continents.

During lyssavirus surveillance, 1,221 bats of at least 30 species were collected from 25 locations in Kenya. One isolate of Lagos bat virus (LBV) was obtained from a dead Eidolon helvum fruit bat. The virus was most similar phylogenetically to LBV isolates from Senegal (1985) and from France (imported from Togo or Egypt; 1999), sharing with these viruses 100% nucleoprotein identity and 99.8 to 100% glycoprotein identity. This genome conservancy across space and time suggests that LBV is well adapted to its natural host species and that populations of reservoir hosts in eastern and western Africa have sufficient interactions to share pathogens. High virus concentrations, in addition to being detected in the brain, were detected in the salivary glands and tongue and in an oral swab, suggesting that LBV is transmitted in the saliva. In other extraneural organs, the virus was generally associated with innervations and ganglia. The presence of infectious virus in the reproductive tract and in a vaginal swab implies an alternative opportunity for transmission. The isolate was pathogenic for laboratory mice by the intracerebral and intramuscular routes. Serologic screening demonstrated the presence of LBV-neutralizing antibodies in E. helvum and Rousettus aegyptiacus fruit bats. In different colonies the seroprevalence ranged from 40 to 67% and 29 to 46% for E. helvum and R. aegyptiacus, respectively. Nested reverse transcription-PCR did not reveal the presence of viral RNA in oral swabs of bats in the absence of brain infection. Several large bat roosts were identified in areas of dense human populations, raising public health concerns for the potential of lyssavirus infection.

Bat rabies and its transmission to humans and other species in Mexico were investigated. Eighty-nine samples obtained from rabid livestock, cats, dogs, and humans in Mexico were studied by antigenic typing and partial sequence analysis. Samples were further compared with enzootic rabies associated with different species of bats in the Americas. Patterns of nucleotide variation allowed the definition of at least 20 monophyletic clusters associated with 9 or more different bat species. Several lineages associated with distinctive antigenic patterns were found in rabies viruses related to rabies in vampire bats in Mexico. Vampire bat rabies virus lineages associated with antigenic variant 3 are widely spread from Mexico to South America, suggesting these lineages as the most likely ancestors of vampire bat rabies and the ones that have been moved by vampire bat populations throughout the Americas. Rabies viruses related to Lasiurus cinereus, Histiotus montanus, and some other not yet identified species of the genus Lasiurus were found circulating in Mexico. Long-range dissemination patterns of rabies are not necessarily associated with migratory bat species, as in the case of rabies in Desmodus rotundus and Histiotus montanus. Human rabies was associated with vampire bat transmission in most cases, and in one case, rabies transmission from free-tailed bats was inferred. The occurrence of rabies spillover from bats to domestic animals was also demonstrated. Genetic typing of rabies viruses allowed us to distinguish trends of disease dissemination and to address, in a preliminary fashion, aspects of the complex evolution of rabies viruses in different host-reservoir species.